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Front. Oncol. | doi: 10.3389/fonc.2019.00839

Structural variants as a basis for targeted therapies in hematological malignancies

  • 1University of Münster, Germany
  • 2Medizinische Fakultät, Universität Münster, Germany

Structural variants (SV) are changes in the genomic landscape that can alter gene expression levels and thus lead to disease development. The most common and best studied SVs in hematological malignancies are chromosomal translocations. Here, parts of two genes that are normally on different chromosomes come into close proximity due to a failure in DNA repair. As a consequence, fusion proteins which show a different function and/or cellular localization compared to the two original proteins are expressed, sometimes even at different levels. The identification of chromosomal translocation is often used to identify the specific disease a patient is suffering from.
In addition, SVs such as deletions, duplications, inversions and single nucleotide polymorphisms (SNPs) can occur in hematopoietic cells and lead to their malignant transformations. Changes in the 3D genome structure have also recently been shown to impact disease development. In this review, we describe a variety of SVs occurring in different subtypes of hematological malignancies.
Currently, most therapeutic approaches target fusion proteins which are the cellular product of chromosomal translocations. However, amplifications and SNPs also play a role in disease progression. We present some examples for different types of structural variants and how they are currently targeted.

Keywords: Structural variant (SV), Hematology, targeted therapy, Chromosomal rearrangements, Chromatin structure

Received: 29 May 2019; Accepted: 14 Aug 2019.

Edited by:

Alessandro Isidori, Hematology and Stem Cell Transplant Center, AORMN Hospital, Italy

Reviewed by:

Nelson Hamerschlak, Albert Einstein Israelite Hospital, Brazil
Guru P. Maiti, Oklahoma Medical Research Foundation, United States  

Copyright: © 2019 Schütte, Reusch, Khandanpour and Eisfeld. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Cyrus Khandanpour, Medizinische Fakultät, Universität Münster, Münster, 48149, North Rhine-Westphalia, Germany,